tbuckley/cabot-search huggingface dataset:
Self-reported Sexual Harassment and Subsequent Reporting Among Internal Medicine Residency Trainees in the US
Authors: Elizabeth M. Viglianti, Lisa M. Meeks, Andrea L. Oliverio, Kathleen Tiffany Lee, Theodore J. Iwashyna, Susan T. Hingle
Journal: JAMA Internal Medicine (2023)

This study uses survey data to describe the types of sexual harassment experienced by internal medicine residents, their knowledge of reporting mechanisms, their reporting intentions and actions, and satisfaction with reporting outcomes.
Theranostic Targeting of CUB Domain–Containing Protein 1 (CDCP1) in Multiple Subtypes of Bladder Cancer
Authors: Shalini Chopra, Kai Trepka, Sasank Sakhamuri, Alberto Carretero-González, Jun Zhu, Emily Egusa, Jie Zhou, Kevin Leung, Ning Zhao, Nima Hooshdaran, Felix Y. Feng, James A. Wells, Jonathan Chou, Michael J. Evans
Journal: Clinical Cancer Research (2023)

Despite recent approvals for checkpoint inhibitors and antibody-drug conjugates targeting NECTIN4 or TROP2, metastatic bladder cancer remains incurable and new treatment strategies are urgently needed. CUB domain-containing protein 1 (CDCP1) is a cell surface protein and promising drug target for many cancers. This study aimed to determine whether CDCP1 is expressed in bladder cancer and whether CDCP1 can be targeted for treatment with radiolabeled antibodies.CDCP1 expression was evaluated in four bladder cancer datasets (n = 1,047 biopsies). A tissue microarray of primary bladder cancer biopsies was probed for CDCP1 by IHC. CDCP1 expression was evaluated in patient-derived xenografts and cell lysates by immunoblot, flow cytometry, and saturation binding assays. Tumor detection in mouse bladder cancer models was tested using 89Zr-labeled 4A06, a monoclonal antibody targeting the ectodomain of CDCP1. 177Lu-4A06 was applied to mice bearing UMUC3 or HT-1376 xenografts to evaluate antitumor effects (CDCP1 expression in UMUC3 is 10-fold higher than HT-1376).CDCP1 was highest in the basal/squamous subtype, and CDCP1 was expressed in 53% of primary biopsies. CDCP1 was not correlated with pathologic or tumor stage, metastatic site, or NECTIN4 and TROP2 at the mRNA or protein level. CDCP1 ranged from 105 to 106 receptors per cell. Mechanism studies showed that RAS signaling induced CDCP1 expression. 89Zr-4A06 PET detected five human bladder cancer xenografts. 177Lu-4A06 inhibited the growth of UMUC3 and HT-1376 xenografts, models with high and moderate CDCP1 expression, respectively.These data establish that CDCP1 is expressed in bladder cancer, including TROP2 and NECTIN4-null disease, and suggest that bladder cancer can be treated with CDCP1-targeted radiotherapy.
Association of Sialic Acid–Binding Immunoglobulin-Like Lectin 15 With Phenotypes in Esophageal Squamous Cell Carcinoma in the Setting of Neoadjuvant Chemoradiotherapy
Authors: Sha Zhou, Yuting Wang, Rui Zhang, Weian Zeng, Shiliang Liu, Songran Liu, Mengzhong Liu, Hong Yang, Mian Xi
Journal: JAMA Network Open (2023)

Importance Sialic acid–binding immunoglobulin-like lectin 15 (Siglec-15) is a novel immune checkpoint molecule that is highly homologous to programmed cell death ligand 1 (PD-L1), but information remains limited about its role in esophageal squamous cell carcinoma (ESCC). Objective To explore the expression pattern and association of Siglec-15 with outcomes among patients with ESCC who received neoadjuvant chemoradiotherapy (CRT). Design, Setting, and Participants This retrospective cohort study was conducted at an academic institution in China. Participants included patients with ESCC who underwent neoadjuvant CRT and esophagectomy between June 2002 and December 2018. Multiplexed immunofluorescence staining was used to evaluate the expression of Siglec-15 and PD-L1 in tumor cells (TCs) or tumor-associated macrophages based on pre-CRT biopsies. Different immune phenotypes have been proposed and further validated in an independent cohort. Data analysis was conducted from January to May 2021. Exposures Siglec-15 or PD-L1 positivity vs negativity. Main Outcomes and Measures Pathologic complete response (pCR), overall survival (OS), and recurrence-free survival (RFS). Results Of 130 participants (median [range] age, 56 [42-73] years; 108 [83.1%] male participants) in the primary cohort, 58 patients (44.6%) achieved a pCR after neoadjuvant CRT. Siglec-15 and PD-L1 were detected in both TCs and macrophages. The percentage of Siglec-15–positive macrophages was notably higher than that of Siglec-15–positive TCs (median [IQR]: 34.4% [12.7%-64.3%] vs 4.8% [0.7%-25.6%]; P &amp;amp;lt; .001). TC–Siglec-15 expression was significantly and positively associated with macrophage–Siglec-15 expression ( r = 0.78; P &amp;amp;lt; .001). Siglec-15 positivity was significantly associated with a higher rate of pCR (37 of 70 [52.9%] vs 21 of 60 [35.0%]; P = .04), more favorable OS (hazard ratio [HR], 0.46; 95% CI, 0.25-0.85; P = .01), and RFS (HR, 0.48; 95% CI, 0.26–0.88; P = .02). However, PD-L1 positivity in TCs was negatively associated with survival. Stratification analysis further revealed that patients with combined Siglec-15 positivity and PD-L1 negativity had better survival than those with other phenotypes. Major findings were reproducible in a validation cohort with 55 patients. Conclusions and Relevance In this cohort study of patients with ESCC receiving neoadjuvant CRT, Siglec-15 positivity was associated with a better pathological response and more favorable survival. Siglec-15 could serve as a novel biomarker to identify potential candidates that may benefit from immunotherapy combined with CRT.
New Screening Tool for Term-Born Infants Enables Update to the Clinical Practice Guideline for Early Diagnosis of Cerebral Palsy
Authors: Toohey Monica, Morgan Catherine, Novak Iona
Journal: JAMA Pediatrics (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Development of a Bedside Tool to Predict the Diagnosis of Cerebral Palsy in Term-Born Neonates
Authors: Amira Rouabhi, Nafisa Husein, Deborah Dewey, Nicole Letourneau, Thierry Daboval, Maryam Oskoui, Adam Kirton, Michael Shevell, Mary J. Dunbar, John Anderson, David Buckley, Darcy Fehlings, Lee Burkholder, Louise Koclas, Nicole Pigeon, Esias Van Rensburg, Jordan Sheriko, Ellen Wood
Journal: JAMA Pediatrics (2023)

Cerebral palsy (CP) is the most common abnormality of motor development and causes lifelong impairment. Early diagnosis and therapy can improve outcomes, but early identification of infants at risk remains challenging.
Corticosteroids and Cancer Immunotherapy
Authors: Rachel S. Goodman, Douglas B. Johnson, Justin M. Balko
Journal: Clinical Cancer Research (2023)

Abstract Despite revolutionizing cancer management, immunotherapies dysregulate the immune system, leading to immune-mediated adverse events. These common and potentially dangerous toxicities are often treated with corticosteroids, which are among the most prescribed drugs in oncology for a wide range of cancer and noncancer indications. While steroids exert several mechanisms to reduce immune activity, immunotherapies, such as immune checkpoint inhibitors (ICI), are designed to enhance the immune system's inherent antitumor activity. Because ICI requires an intact and robust immune response, the immunosuppressive properties of steroids have led to a widespread concern that they may interfere with antitumor responses. However, the existing data of the effect of systemic steroids on immunotherapy efficacy remain somewhat conflicted and unclear. To inform clinical decision-making and improve outcomes, we review the impact of steroids on antitumor immunity, recent advances in the knowledge of their impact on ICI efficacy in unique populations and settings, associated precautions, and steroid-sparing treatment approaches.
More Adolescents and Young Adults Developing Type 2 Diabetes Around the World
Authors: Howard Larkin
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Caution With Conclusions and Context of Mechanical Circulatory Devices—Reply
Authors: P. Elliott Miller, Nihar R. Desai
Journal: JAMA Internal Medicine (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Serum Urate–Lowering Efficacy and Safety of Tigulixostat in Gout Patients With Hyperuricemia: A Randomized, <scp>Double‐Blind</scp>, <scp>Placebo‐Controlled</scp>, <scp>Dose‐Finding</scp> Trial
Authors: Robert Terkeltaub, Jisoo Lee, Jiyoung Min, Seonghye Shin, Kenneth G. Saag
Journal: Arthritis & Rheumatology (2023)

To evaluate the safety and efficacy of the nonpurine xanthine oxidase inhibitor tigulixostat for lowering serum urate level in gout patients with hyperuricemia.We conducted a multicenter, phase II, randomized, double-blind, placebo-controlled, parallel-group, dose-finding trial. After screening, gout patients with hyperuricemia were randomly assigned, after appropriate washout, to receive daily oral administration of 50 mg, 100 mg, or 200 mg of tigulixostat, or placebo for 12 weeks. Colchicine gout flare prophylaxis was administered to all patients. The primary end point was the proportion of patients with a serum urate level <5.0 mg/dl at week 12.A total of 143 patients were randomized to receive tigulixostat 50 mg (n = 34), 100 mg (n = 38), or 200 mg (n = 37), or placebo (n = 34). A significantly greater proportion of patients in the tigulixostat groups achieved the target serum urate level <5.0 mg/dl at week 12 (47.1% in the 50 mg group, 44.7% in the 100 mg group, and 62.2% in the 200 mg group) compared to the placebo group (2.9%) (P < 0.0001). The mean percentage change in serum urate level from baseline was also significantly greater in the tigulixostat groups (-38.8% to -61.8%) than in the placebo group at all time points (P < 0.0001). The rate of gout flares requiring rescue treatment ranged from 9.4% to 13.2% in the tigulixostat and placebo groups. The incidence of adverse events was 50.0% to 56.8% across all groups, and their severity was mild or moderate.Tigulixostat significantly lowered serum urate compared to placebo at all doses studied with an acceptable safety profile.
TRANSFORM-HF—Can We Close the Loop on Diuretics in Heart Failure?
Authors: Michelle M. Kittleson
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The Development of Drug Delivery Systems for Efficient Intracranial Hemorrhage Therapy
Authors: Wenyan Yu, Bingbing Liu, Lei Zhou, Enpeng Gong, Chengyuan Che, Jianchao Zhou, Zhenzhong Zhang, Junjie Liu, Jinjin Shi
Journal: Advanced Healthcare Materials (2023)

Abstract Intracerebral hemorrhage (ICH) is the most devastating form of stroke, which accounts for 10–15% of cases and causes high morbidity and mortality. With the continuous exploration of the pathological mechanism of ICH, extensive research focusing on ICH therapy has been conducted. However, the traditional treatment methods, such as surgery for removing the hematoma and pharmacotherapy for improving the clearance of the hematoma and neuroprotection, are greatly limited due to their poor practicality and treatment efficiency. The rapid development of drug delivery systems offers an important prospect for treating ICH as they exhibit great versatility, which can improve the pharmacokinetic behavior of drugs in vivo, increase the drug accumulation in specific cell types or tissues, and enhance the therapeutic effect with diminished toxic effect. In this review, the main molecular pathological mechanisms of ICH are comprehensively described and the limitation of traditional pharmacotherapy are also discussed. Then the development based on drug delivery systems for treating ICH is highlighted. Finally, based on these discussions the challenges of drug delivery systems with a view to providing a new feasible path for the treatment of ICH are summarized.
Analysis of Rates of Completion, Delays, and Participant Recruitment in Randomized Clinical Trials in Surgery
Authors: Cade Shadbolt, Elise Naufal, Samantha Bunzli, Veronique Price, Siddharth Rele, Chris Schilling, Sharmala Thuraisingam, L. Stefan Lohmander, Zsolt J. Balogh, Philip Clarke, Peter Choong, Michelle Dowsey
Journal: JAMA Network Open (2023)

Importance Discontinuation and nonpublication are established sources of avoidable waste among surgical trials, but rates of delayed completion and recruiting shortfalls remain unclear. Objectives To examine the rate of delayed completion, incomplete enrollment, and discontinuation among randomized clinical trials in surgical populations and the duration of delays and extent of recruiting shortfalls among these trials. Design, Setting, and Participants This cross-sectional study examined randomized clinical trials in surgical populations registered on ClinicalTrials.gov between January 1, 2010, and December 31, 2014. Analysis was conducted between October 27, 2021, and June 30, 2022. Main Outcomes and Measures The main outcomes were the percentages of trials completed on time or with full enrollment. Delays and recruiting shortfalls were identified by comparing projected enrollment and study timeframes prespecified at the time of registration with the actual study duration and enrollment reported on completion or discontinuation. Absolute and relative differences between planned and actual trial conduct were presented for discontinued trials and those completed with delays or recruiting shortfalls. Results In total, 2542 randomized clinical trials in surgical populations were included in the study sample, of which 370 (14.6%; 95% CI, 13.2%-15.9%) were completed both on time and with full enrollment. Approximately 1 in 5 trials (20.4%; 95% CI, 18.9%-22.0%) were completed within their planned timeframe, and 1166 trials (45.9%; 95% CI, 43.9%-47.8%) met their prespecified enrollment target. The median delay among completed trials was 12.2 months (IQR, 5.1-24.3 months) or 66.7% (IQR, 30.1%-135.8%) longer than planned. Among completed trials that did not meet their prespecified enrollment target, the median recruiting shortfall was equivalent to 31.0% (IQR, 12.7%-55.5%) of the planned study sample. A total of 546 trials (21.5%; 95% CI, 19.9%-23.1%) were discontinued. The median time to discontinuation was 26.4 months (IQR, 15.2-45.7 months), and the median recruiting shortfall among discontinued trials was equivalent to 92.7% (IQR, 65.0%-100.0%) of the trial’s prespecified enrollment target. Conclusions and Relevance This cross-sectional study found that delayed completion, recruiting shortfalls, and untimely discontinuation were common among surgical trials. These findings highlight the importance of ensuring that investigators and funders do not overestimate the feasibility of planned trials.
Error in Figure
Authors: Håkon Vegrim, Torbjörn Tomson, Marte-Helene Bjørk
Journal: JAMA Neurology (2023)

Shorena Janelidze, PhD; Charlotte E. Teunissen, PhD; Henrik Zetterberg, MD, PhD; José Antonio Allué, PhD; Leticia Sarasa, PhD; Udo Eichenlaub, PhD; Tobias Bittner, PhD; Vitaliy Ovod, MSs; Inge M. W. Verberk, MSs; Kenji Toba, MD, PhD; Akinori Nakamura, MD, PhD; Randall J. Bateman, MD, PhD; Kaj Blennow, MD, PhD; Oskar Hansson, MD, PhD
Longitudinal Developmental Outcomes of Infants and Toddlers With Traumatic Brain Injury
Authors: Heather T. Keenan, Amy Clark, Rich Holubkov, Linda Ewing-Cobbs
Journal: JAMA Network Open (2023)

Importance Among children, infants and toddlers have some of the highest rates of traumatic brain injury (TBI), but longitudinal information on their developmental outcomes to guide postinjury surveillance is sparse. Objective To evaluate infants’ and toddlers’ development over 3 years following TBI compared with those with orthopedic injury (OI). Design, Setting, and Participants A longitudinal observational cohort study was conducted at 2 level 1 pediatric trauma centers from January 20, 2013, to September 30, 2015; data analysis was performed from May 12 to October 20, 2021. Participants included children injured when younger than 31 months with TBI or OI who received emergency department care. Exposures Mild, moderate, or severe TBI or OI. Main Outcomes and Measures Parents completed baseline measures representing preinjury status and 3-, 12-, 24-, and 36-month postinjury status, using the Ages &amp;amp;amp; Stages Questionnaire-3 (ASQ-3), with a mean reference value of 50 and higher scores indicating more advanced development. Linear mixed models characterized children’s outcomes for each ASQ-3 domain after adjustment for baseline ASQ-3, injury severity and group, age, injury mechanism (abuse or not), sex, prematurity, family function, social capital, and time. Interactions with time were evaluated. Results Consent for participation was provided for 195 children; 184 parents (94%) completed a baseline survey. The cohort included 168 children who completed at least 1 follow-up survey: 48 (29%) mild; 54 (32%) complicated mild/moderate; 21 (13%) severe TBI; and 45 (27%) orthopedic injury. The cohort included 95 boys (57%), 49% injured before age 1 year; and 13% injured by abuse. Mean (SD) age at the time of injury was 13.9 (9.4) months. At 36 months, children with mild or complicated mild/moderate TBI performed similarly to children with OI across ASQ-3 domains. Children with severe TBI performed poorly as shown by negative mean differences in communication (–8.8; 95% CI, –13.8 to –3.8); gross motor (–10.1; 95% CI, –15.1 to –5.1); problem solving (–6.6; 95% CI, –11.2 to –1.9), and personal social (–6.3; 95% CI, –10.4 to –2.1) domains with little recovery over time. Children with abusive injury experienced decrements in ability over time in fine motor and personal social skills. Social capital was protective in communication (mean, 1.5; 95% CI, 0.3-2.7) and problem solving (mean, 1.2; 95% CI, 0.1-2.3) domains. Conclusions and Relevance In this cohort study of children with TBI, children with severe injury showed little recovery. These findings suggest that early childhood intervention is needed, while children with milder injury remained on their developmental track and should continue routine developmental surveillance.